Nevus-associated Melanoma Research Articles

Clinical implication of PRAME immunohistochemistry in differentiating melanoma in situ and dysplastic nevus in non-acral nevus-associated melanoma in situ: An institutional experience and meta-analysis.

PReferentially expressed Antigen in MElanoma (PRAME) has shown utility in differentiating benign from malignant melanocytic neoplasms. In this study, we investigated the clinical significance of PRAME expression in dysplastic nevi (DN) and nevus-associated melanoma in situ (MIS). We included 172 DN and 38 nevus-associated MIS from our institutional archive. PRAME positive expression was defined as nuclear staining in at least 75% of melanocytes. In addition, relevant studies from PubMed and Web of Science were incorporated into a meta-analysis using the random-effects model to assess PRAME expression in MIS and DN. Our institutional data revealed that 71.1% of nevus-associated MIS cases exhibited positive PRAME expression in the MIS components, whereas all DN components were negative for PRAME. 5.7% of cases diagnosed as DN in our cohort demonstrated diffuse positivity for PRAME. Notably, MIS associated with DN displaying epidermal and dermal components displayed a higher likelihood of PRAME positivity compared to those arising on a background of DN with solely epidermal (junctional) components (84% vs. 46%, p = 0.024). The meta-analysis indicated that the pooled PRAME positivity in MIS and DN was 54.5% and 1.9%, respectively. PRAME is a valuable immunohistochemical marker for differentiating MIS from DN, particularly in the context of nevus-associated MIS.

Comparative Quantitative Proteomic Analysis of Melanoma Subtypes, Nevus-Associated Melanoma, and Corresponding Nevi

A substantial part of cutaneous malignant melanomas develops from benign nevi. However, the precise molecular events driving the transformation from benign to malignant melanoma are not well understood. We used laser microdissection and mass spectrometry to analyze the proteomes of melanoma subtypes, including superficial spreading melanomas (SSM, n=17), nodular melanomas (NM, n=17), and acral melanomas (AM, n=15). Furthermore, we compared the proteomes of nevi cells and melanoma cells within the same specimens (nevus-associated melanoma (NAM, n=14)). In total, we quantified 7,935 proteins.Despite the genomic and clinical differences of the melanoma subtypes, our analysis revealed relatively similar proteomes, except for the upregulation of proteins involved in immune activation in NM vs AM. Examining NAM versus nevi, we found 1,725 differentially expressed proteins (FDR < 0.05). Among these proteins were 140 that overlapped with cancer hallmarks, tumor suppressors, and regulators of metabolism and cell cycle. Pathway analysis indicated aberrant activation of the PI3K-AKT-mTOR pathways and the Hippo-YAP pathway. Using a classifier, we identified six proteins capable of distinguishing melanoma from nevi samples. Our study represents a comprehensive comparative analysis of the proteome in melanoma subtypes and associated nevi, offering, to our knowledge, previously unreported insights into the biological behavior of these distinct entities.

Melanoma in children: A systematic review and individual patient meta-analysis.

The current evidence on paediatric melanoma is heterogeneous, especially regarding the prognosis of different histological subtypes. We sought to systematically review the evidence on paediatric melanoma, highlighting the major sources of heterogeneity and focusing on available data on single patients. A systematic search was performed from 1948 to 25 January 2021. Only studies reporting at least one case of cutaneous melanoma in patients aged ≤18 years were included. Unknown primary and uncertain malignant melanomas were excluded. Three couples of authors independently performed title/abstract screening and two different authors reviewed all the relevant full texts. The selected articles were manually cross-checked for overlapping data for qualitative synthesis. Subsequently data on single patients were extracted to perform a patient-level meta-analysis. PROSPERO registration number: CRD42021233248. The main outcomes were melanoma-specific survival (MSS) and progression-free survival (PFS) outcomes. Separate analyses were done of cases with complete information on histologic subtype, focusing on superficial spreading (SSM), nodular (NM) and spitzoid melanomas, as well as of those classified as de-novo (DNM) and acquired or congenital nevus-associated melanomas (NAM). The qualitative synthesis covered 266 studies; however, data on single patients were available from 213 studies including 1002 patients. Among histologic subtypes, NM had a lower MSS than both SSM and spitzoid melanoma, and a lower PFS than SSM. Spitzoid melanoma had a significantly higher progression risk than SSM and trended toward lower mortality. Focusing on nevus-associated status, DNM demonstrated better MSS after progression than congenital NAM, and no differences were highlighted in PFS. Our findings describe the existence of different biological patterns in paediatric melanoma. Specifically, spitzoid melanomas demonstrated intermediate behaviour between SSM and NM and showed a high risk of nodal progression but low mortality. This raises the question of whether spitzoid lesions are being over-diagnosed as melanoma in childhood.

The Association of Nevus-Associated Melanoma with Common or Dysplastic Melanocytic Nevus: A Systematic Review and Meta-Analysis.

Background: Cutaneous melanoma has an adjacent nevus remnant upon histological examination in 30% of cases (nevus-associated melanoma, NAM), while it appears de novo for 70% of tumors. Regarding NAM arising in acquired melanocytic nevus, currently there is no evidence on whether NAM more frequently develops in association with a dysplastic or common melanocytic nevus. Objectives: To conduct a systematic review and meta-analysis to investigate the proportion of dysplastic or common melanocytic nevus in NAM associated with acquired nevus. Methods: A systematic literature search is conducted using PubMed, Scopus, and the Cochrane Library. The PRISMA checklist is used. Studies reporting patients diagnosed with NAM arising in an acquired common or dysplastic melanocytic nevus are included. A meta-analysis of proportions is performed using the random-effects model. The magnitude of heterogeneity is assessed with the I2 statistic. Results: A total of 22 studies with 2174 NAMs with an acquired nevus (dysplastic or common) are included. The proportion of dysplastic nevus in NAM varies considerably in the included studies, ranging from 0% to 100%. In the meta-analysis, the overall estimate of the proportion of having a dysplastic nevus in NAM is 51% (95% CI: 39-63%) with high heterogeneity at I2: 95.8% (p < 0.01). A sensitivity meta-analysis of 12 studies that included 30 or more acquired nevus-NAMs (2023 cases) shows that 65% of the NAMs developed in a dysplastic nevus (95% CI: 51-77%). In a meta-analysis of 4 studies reporting invasive-only acquired nevus-NAMs (764 cases), the proportion of dysplastic nevus is 56% (95% CI: 36-75%). Only 2 studies are found reporting in situ NAMs with an acquired nevus, and the pooled estimated proportion of dysplastic nevus is 71% (95% CI: 63-78%). Conclusions: The results of this meta-analysis suggest a higher proportion of dysplastic nevus in acquired nevus-NAM; however, there is considerable uncertainty and high heterogeneity, highlighting the need for future well-designed studies with uniform histopathological definitions for dysplastic nevus remnants which report the type of nevus in NAM separately for invasive melanomas, thin tumors, and by histological subtype.

Review: The Key Factors to Melanomagenesis.

Melanoma is the most dangerous form of skin cancer that develops from the malignant transformation of the melanocytes located in the basal layer of the epidermis (cutaneous melanoma). Melanocytes may also be found in the meninges, eyes, ears, gastrointestinal tract, genito-urinary system, or other mucosal surfaces (mucosal melanoma). Melanoma is caused by an uncontrolled proliferation of melanocytes, that at first may form a benign lesion (nevogenesis), but in time, it may transition to melanoma, determining what it is named, melanomagenesis. Some tumors may appear spontaneously (de novo melanoma) or on preexisting lesions (nevus-associated melanoma). The exact cause of melanoma may not be fully understood yet, but there are some factors that initiate and promote this malignant process. This study aims to provide a summary of the latest articles regarding the key factors that may lead to melanomagenesis. The secondary objectives are to reveal the relationship between nevi and melanoma, to understand the cause of "de novo" and "nevus-associated melanoma" and highlight the differences between these subtypes.

A review of nevus-associated melanoma: What is the evidence?

Cutaneous melanoma may have an adjacent nevus remnant on histological examination in 30% of cases (nevus-associated melanoma, NAM), while it may appear de novo, without a precursor lesion, in the remaining 70% of cases. Nevus-associated melanoma and the concept of acquired melanocytic nevi serving as precursors of melanoma has long been considered as a controversial topic. This controversy is, in part, due to their overall low rate of transformation to melanoma and scarce data on the natural history of progression. Another matter of debate regarded the possibility that the reported differences in NAM vs. de novo melanoma were due to an underestimation of NAM in thicker lesions due to obliteration of the nevus component by the tumour. During the last few years, several evidence has accumulated in order to address these controversies. In this review, we present a comprehensive synthesis of the epidemiological, clinical, dermoscopic and genetic findings in NAM, including thin NAM, compared to de novo melanoma. Answering the questions on nevus-associated melanoma may provide further insight into the classification of these tumours and disentangle their biology and route of development from that of de novo melanoma.

The EORTC protocol for sentinel lymph node biopsy (SLNB) reveals a high number of nodal nevi and a strong association with nevus-associated melanoma

BackgroundThe diagnosis of nodal nevi (NN) is challenging as they mimic melanoma metastases (MM), with a detection rate mostly ranging between 1% and 11% in sentinel lymph node biopsy (SLNB). Herein, we assessed the incidence of NN and the association with the clinical-pathological features of primary melanoma, adopting the updated European Organisation for Research and Treatment of Cancer (EORTC) protocol for SLNB. MethodsAll cases of paired melanoma and SLNB were retrospectively evaluated (April 2019-May 2020). Appropriate statistical tests were adopted, with significant variables included in the logistic regression model. Results81 patients and a total of 186 lymph nodes (LNs) were included. Eleven patients had only NN and 4 had both NN and MM (18.5%); 29 LNs (15.6%) showed at least one NN and 12 (6.5%) showed more than one NN (a total amount of 43 NN was detected). All NN and none MM stained for p16. NN were associated with age < 60 years (p: 0.042), no ulceration (p: 0.025) and nevus-associated melanoma (NAM) (p: 0.018), with this latter being the only predictor at the logistic regression model (p: 0.022). ConclusionsThe updated EORTC protocol shows a high number of NN and highlights a strong association with NAM.

Dermoscopic Criteria, Histopathological Correlates and Genetic Findings of Thin Melanoma on Non-Volar Skin.

Dermoscopy is a non-invasive, in vivo technique that allows the visualization of subsurface skin structures in the epidermis, at the dermoepidermal junction, and in the upper dermis. Dermoscopy brought a new dimension in evaluating melanocytic skin neoplasms (MSN) also representing a link between clinical and pathologic examination of any MSN. However, histopathology remains the gold standard in diagnosing MSN. Dermoscopic–pathologic correlation enhances the level of quality of MSN diagnosis and increases the level of confidence of pathologists. Melanoma is one of the most genetically predisposed among all cancers in humans. The genetic landscape of melanoma has been described in the last years but is still a field in continuous evolution. Melanoma genetic markers play a role not only in melanoma susceptibility, initiation, and progression but also in prognosis and therapeutic decisions. Several studies described the dermoscopic specific criteria and predictors for melanoma and their histopathologic correlates, but only a few studies investigated the correlation among dermoscopy, pathology, and genetic of MSN. The aim of this work is to review the published data about dermoscopic features of melanoma, their histopathological correlates with regards also to genetic alterations. Particularly, this review will focus on low-CSD (cumulative sun damage) melanoma or superficial spreading melanoma, high-CSD melanoma, and nevus-associated melanoma.

Unsupervised Phenotype-Based Clustering of Clinicopathologic Features in Cutaneous Melanoma

Pathogenic phenotypes in cutaneous melanoma have been vastly cataloged, although these classifications lack concordance and are confined to either morphological or molecular contexts. In this study, we perform unsupervised k-medoids clustering as a machine learning technique of 2,978 primary cutaneous melanomas at Mass General Brigham and apply this information to elucidate computer-defined subsets within the clinicopathologic domain. We identified five optimally separated clusters of melanoma that occupied two distinct clinicopathologic subspaces: a lower-grade partition associated with common or dysplastic nevi (i.e., nevus-associated melanomas) and a higher-grade partition lacking precursor lesions (i.e., de novo melanomas). Our model found de novo melanomas to be more mitogenic, more ulcerative, and thicker than nevus-associated melanomas, in addition to harboring previously unreported differences in radial and vertical growth phase status. The utilization of mixed clinicopathologic variables, reflective of actual clinical data contained in surgical pathology reports, has the potential to increase the biological relevance of existing melanoma classification schemes and facilitate the discovery of new genomic subtypes.

The differences in clinical and dermoscopic features between in situ and invasive nevus-associated melanomas and de novo melanomas.

Nevus-associated melanomas (NAM) account for 30% of all melanomas and are associated with younger age and with thinner Breslow thickness. Previous studies of NAM dermoscopy found conflicting results. To compare the clinical and dermoscopic features of NAM and de novo melanomas (DNM), stratified by melanoma thickness, in a relatively large cohort of patients. A cross-sectional study of all melanomas biopsied between 2004 and 2019 at a large cancer centre. Lesions were categorized as in situ and invasive NAM or DNM. Dermoscopic images were reviewed and annotated. Associations between melanoma subtype and dermoscopic features were analysed via logistic regression modelling. Bivariate analyses were conducted using non-parametric bootstrap and chi-squared methods. The study included 160 NAM (86 in situ and 74 invasive) and 218 DNM (109 in situ and 109 invasive). NAM were associated with younger age, greater likelihood of being present on the torso, and thinner Breslow thickness. NAM were 2.5 times more likely to show a negative pigment network than DNM. In situ NAM were 2.1 and two times more likely to display dermoscopic area without definable structures and tan structureless areas than DNM, respectively. In situ melanomas were more likely to present a pigment network, and invasive melanomas more commonly presented scar-like depigmentation and shiny white structures. Streaks, blotches and shiny white structures were associated with deeper Breslow depth. Even though the nevus component of NAM could not be identified dermoscopically in the current series, negative pigment network, tan structureless areas and areas without definable structures are dermoscopic clues for NAM.

Coexistence of regression and tumor infiltrating lymphocytes is associated with more favorable survival in melanoma

Melanoma is one of the highly immunogenic malignancies, and histological regression (HR) and tumor infiltrating lymphocytes (TILs) represent early signs of activation of the immune system against primary melanoma. In this study we aimed to investigate the potential roles of HR and TILs on survival, as combined or separately. A total of 916 cutaneous melanomas were analyzed retrospectively. Only minority of the lesions had HR (25.1%) and they were associated with males (p = 0.002), axial localization (p = 0.0001), non-nodular histopathology (p = 0.0001), thin Breslow depth (p = 0.01) and nevus-associated melanoma (p = 0.03). Those with TILs (48.4%) were found in association with lower Clark levels (p = 0.003), thin tumor thicknesses (p = 0.001), lower mitotic rates (p = 0.02), BRAF mutation (p = 0.03), absence of neurotropism (p = 0.03), involvement of lymph node (p = 0.0001) and relapse of disease (p = 0.04). A significant relationship was found between HR and TILs (p = 0.01). TILs were independently associated with favorable RFS (p = 0.02), whereas no relationship was observed between HR and RFS (p = 0.2). A marked favorable survival advantage was noted in the group with HR (+)/TILs (+) compared to other groups with HR (-)/TILs (-) (p = 0.007), only HR (+) and only TILs (+). Both HR (p = 0.05) and TILs (p = 0.04) were correlated with favorable OS rates. Moreover, HR (+) /TILs (+) patients had more favorable OS than other groups with HR (-)/TILs (-) (p = 0.002), only HR (+) and only TILs (+). Only HR (+) and only TILs (+) subgroups separately were found to be associated with favorable survivals in melanoma. Furthermore, coexistence of HR and TILs, HR (+)/TILs (+) subgroup, had more favorable survival rates compared to only HR (+) and only TILs (+) subgroups.

Influence of germline genetic variants on dermoscopic features of melanoma.

Nevus count is highly determined by inherited variants and has been associated with the origin of melanoma. De novo melanomas (DNMMs) are more prevalent in patients with a low nevus count and have distinctive dermoscopic features than nevus-associated melanomas. We evaluated the impact of nine single nucleotide polymorphisms (SNPs) of MTAP (rs10811629, rs2218220, rs7023329 and rs751173), PLA2G6 (rs132985 and rs2284063), IRF4 (rs12203592), and PAX3 (rs10180903 and rs7600206) genes associated with nevus count and melanoma susceptibility, and the MC1R variants on dermoscopic features of 371 melanomas from 310 patients. All MTAP variants associated with a low nevus count were associated with regression structures (peppering and mixed regression), blue-whitish veil, shiny white structures, and pigment network. SNPs of PLA2G6 (rs132985), PAX3 (rs7600206), and IRF4 (rs12203592) genes were also associated with either shiny white structures or mixed regression (all corrected p-values≤.06). Melanomas from red hair color MC1R variants carriers showed lower total dermoscopy score (p-value=.015) and less blotches than melanomas from non-carriers (p-value=.048). Our results provide evidence that germline variants protective for melanoma risk and/or associated with a low nevus count are associated with certain dermoscopic features, more characteristic of de novo and worse prognosis melanomas.

De Novo and Nevus-Associated Melanomas: Different Histopathologic Characteristics but Similar Survival Rates.

The clinical significances of de novo and nevus-associated melanomas are controversial. In this study, we investigated the correlations of these forms of melanomas in respect to their pathological and clinical features and patient outcomes. The data of 660 pathologically confirmed Turkish-Caucasian melanoma patients, whose tumors were either associated with a pre-existing melanocytic nevus or not, were analyzed retrospectively. They were treated and followed up at a single tertiary referral center. A total of 440 de novo (66.7%) and 220 nevus-associated melanomas (33.3%) were enrolled into the study. The median age of the patients was 51years. The patients consisted of 341 men (51.7%) and 319 women (48.3%). There were significant correlations between de novo melanomas and advanced age (p = 0.003), tumor thickness greater than 2mm (p = 0.0001), ulceration (p = 0.01) and high mitotic rate (p = 0.03). On the other hand, nevus-associated melanomas were found significantly associated with histological regression (p = 0.03) and BRAFV600E mutation (p = 0.003). Most of the nevus-associated melanomas were found on trunk and head/neck, whereas extremities were more frequently inflicted by de novo melanomas (p = 0.0001). Furthermore, none of other variables, such as sex, histopathology, lymph node involvement and presence of metastasis, showed statistically significant difference between de novo and nevus-associated melanoma patients (p > 0.05). The 5-year DFS rates were 62.4% and 72.7% for de novo melanoma and for nevus-associated melanoma patients, respectively (p = 0.1). The 5-year OS rate were 72.1% and 76.4% for de novo melanoma and nevus-associated melanoma patients, respectively (p = 0.2). In conclusion, even though de novo melanomas are more significantly correlated with aggressive histopathologic variables, such as tumor depth, ulceration and high mitotic rate, the survival rates of de novo and nevus-associated melanomas are similar.

Digital dermoscopic changes during follow-up of de-novo and nevus-associated melanoma: a cohort study.

Nevus-associated melanoma (NAM) has been regarded as a distinct biological entity from de-novo melanoma (DNM); however, static dermoscopy often fails in differentiating these entities. Digital dermoscopic monitoring allows to identify dynamic changes occurring during follow-up; this may improve diagnostic accuracy and potentially our knowledge on NAM biology. We aimed to define main independent factors associated with NAM diagnosis and those influencing follow-up time in a population of melanomas excised at follow-up. A cohort of melanomas excised at follow-up was retrospectively and consecutively selected. NAMs and DNMs were compared according to baseline features and main dermoscopic changes occurring during follow-up. Univariate and multivariable logistic and Cox's regression analysis were performed to respectively define factors associated with NAM diagnosis and those influencing the risk for excision. Eighty-six melanomas were enrolled, of which 21 (24.4%) were nevus-associated. During follow-up NAMs mainly underwent atypical network modifications (47.6%), followed by inverse network (28.6%) and dermoscopic island (23.8%) worsening or appearance. DNMs were also mainly characterized by atypical network modifications (47.7%), however, a significant proportion of cases underwent irregular pigmentation/dots/globules or regression changes (29.2%), which were rarely seen among NAMs. Furthermore, both multivariable logistic and Cox's regression analysis demonstrated a significant association between NAM and a longer follow-up. We demonstrated that among melanomas excised at follow-up, different patterns of dermoscopic changes may be found between NAMs and DNMs. This finding, together with the association of NAM with a longer follow-up time, supports the hypothesis of different biological behavior of these two entities.

Clinical and dermoscopic characteristics of congenital and noncongenital nevus-associated melanomas

Nospecific features of nevus-associated melanoma (NAM) are currently defined. To identify clinical/dermoscopic features of NAM. Retrospective evaluation of histopathologically diagnosed NAM. Eighty of 165 NAMs had a clinically recognizable nevus component, often raised or nodular, most frequently characterized by different morphologic clones and/or colors. In 111 of 165 NAMs, dermoscopy showed a nevus component, prevalently characterized by regular dots/clods and structureless brown areas. Clinically, the melanoma component was eccentric/peripheral in 45 of 80 cases and central in 35 of 80; dermoscopically, the figures were 59 of 111 and 52 of 111, respectively. Melanomas associated with congenital nevi (C-NAMs) occur at a younger age and have a thicker Breslow depth than melanomas associated with acquired nevi (NC-NAMs). Dermoscopically, regular dots/globules characterize C-NAMs, and hypopigmented structureless areas characterize NC-NAMs. Retrospective analysis. C-NAMs are more often central to a congenital nevus, with a clod/globular or structureless brown pattern, typical of young patients. NC-NAMs are frequently hypopigmented nodules/plaques, eccentric/peripheral, with hypopigmented structureless areas, typical of older patients.

Potential association between oral mucosal nevus and melanoma: A preliminary clinicopathologic study.

To assess potential association between oral nevi (ON) and nevus-associated melanoma (NAM), in which melanoma cells coexist with nevus cells. A total of 74 ON patients and 7 NAM patients were retrospectively reviewed. Comparative and regression analyses of clinical and histological data were performed between two groups. The mean age of the patients with ON was 36.5years compared with that of 54.7years of the patients with NAM (p=.008). Gender ratio was female predominance for ON (1.64:1 ratio) and male predominance for NAM (6:1 ratio). The most common location of ON and NAM was the palate (31.1%) and gingiva (71.4%), respectively. Univariate regression analysis revealed that elderly male patients (≥60years) with junctional ON located on the gingiva correlate with higher risk of melanoma. Multivariate analysis revealed that junctional type of ON was an independent factor (adjusted OR, 38.32; 95% CI, 3.20-458.64; p=.004) associated significantly with increased risk for melanoma. The preliminary study for the first time elucidated the clinicopathologic features of a Chinese series of ON and evaluated the potential association between ON and NAM with a limited sample size. Further large multicenter studies are needed to confirm the findings.

Is There More Than One Road to Nevus-Associated Melanoma?

The association of melanoma with a preexisting nevus is still a debated subject. Histopathological data support an associated nevus in approximately 30% of all excised melanomas. The annual risk of an individual melanocytic nevus becoming malignant is extremely low and has been estimated to be approximately 0.0005% (or less than 1 in 200,000) before the age of 40 years, to 0.003% (1 in 33,000) in patients older than 60 years. Current understanding, based on the noticeable, small, truly congenital nevi and nevi acquired early in life, is that the first develops before puberty, presents with a dermoscopic globular pattern, and persists for the lifetime, becoming later a dermal nevus in the adult. In contrast, acquired melanocytic nevi develop mostly at puberty and usually undergo spontaneous involution after the fifth decade of life. The purpose of this review is to analyze the data of the literature and to propose, on the basis of epidemiological and clinical-dermoscopic characteristics, a new model of melanogenesis of nevus-associated melanoma.

Nevus-associated melanoma: facts and controversies.

Nevus-associated melanoma (NAM) is defined on histopathological basis by the coexistence of melanoma and nevus components. Melanomas developing on pre-existing congenital or acquired nevi are usually of the superficial spreading subtype and harbor the BRAFV600E mutation. NAM accounts for almost one-third of melanoma cases As compared to de novo melanoma, NAM develops on younger patients, is more frequently located on the trunk, and is associated with a high nevus count, light eye color and history of frequent sunburns. NAM has been regarded as a model to investigate melanoma origin. Molecular analysis defining the mutation profile of NAM's nevus and melanoma components supported the existence of two pathways of melanoma development, the first not involving clinically visible precursors, the second involving melanocytic nevi as precursors. Concerning diagnosis, dermatoscopy may identify nevus and melanoma components when located side-by-side, but no specific criteria have been described when superimposed. In-vivo reflectance confocal microscopy significantly enhances the recognition of NAM by allowing the detection of nevus remnants when superficially located. Regarding prognosis, NAM is generally thinner and more frequently in-situ than de-novo melanoma. Furthermore, studies reporting survival analysis demonstrated a trend towards better overall, distant-metastasis-free and recurrence-free survival. Although a clinical, phenotypic and molecular profile of NAM has been defined, controversies still exist. In the current review, we widely report and discuss facts and controversies on NAM.

Nevus-associated melanoma: An observational retrospective study of 22 patients evaluated with dermoscopy and reflectance confocal microscopy.

The frequency of nevus-associated melanoma (NAM) has been estimated to be 29% of diagnosed melanomas. This is an observational retrospective study of 22 cases of NAM diagnosed in the Universitary Hospital Alcorcón between September 2011 and 2018. The main objective was to analyze dermoscopic and RCM features of NAM. We also studied if there was an association between any dermoscopic or RCM parameter and Breslow depth. The most frequent dermoscopic characteristics were multicomponent pattern (50%), multifocal pigmentation (45.5%), atypical network (59.1%), and blue-gray regression structures (77.3%). RCM evidenced pagetoid cells in 95.5% melanomas (abundant in 59.1%), non-edged dermal papillae in 86.4%, atypical cells at the dermal-epidermal junction in 90.9%, and atypical junctional nesting in 81.8%. Deeper Breslow index was associated with red color (mean Breslow 0.65 vs 0.37 in melanomas without red, P=0.035), shiny white streaks (0.85 vs 0.38, P=0.041), abundant pagetoid cells (0.68 vs 0.26, P=0.017), and non-edged papillae (0.59 vs 0.00, P=0.014). RCM is a valuable tool for diagnosing NAM. Even it is very difficult to differentiate NAM from DNM both with dermoscopy and RCM, RCM can help us to detect remnants of a preexisting nevus and estimate Breslow depth.

The proportion of nevus-associated invasive melanoma differs with Breslow thickness: A cross-sectional study of 1087 cutaneous melanomas

To the Editor: Although most melanomas appear de novo, a third of cases are nevus-associated melanomas (NAMs).1 The proportion of NAMs appears to be slightly higher when the definition is based on information provided by the patient (42%-85%)2,3 than when it is based on the histologic assessment (4%-72%).1-4 One explanation for this discrepancy is the possibility of the tumor destroying the preexisting neval component, a phenomenon that is expected to be seen mostly in thick tumors and, perhaps, in nodular melanomas.